Adenylosuccinate lyase (ADSL) (ADSL)

Adenylosuccinate lyase (ADSL) is a homotetrameric enzyme that plays a critical dual role in purine metabolism, specifically within the de novo purine biosynthetic pathway and the purine nucleotide cycle (Wikipedia, 2024; NIH, 2023). It catalyzes two distinct reactions: the conversion of 5-aminoimidazole-4-(N-succinylcarboxamide) ribotide (SAICAR) to 5-aminoimidazole-4-carboxamide ribotide (AICAR) and the cleavage of adenylosuccinate (S-AMP) into adenosine monophosphate (AMP) and fumarate (Encyclopedia MDPI, 2023). The enzyme's catalytic active site is uniquely formed by the interface of three monomers within the tetramer, making its quaternary structure essential for activity (NIH, 2025). Mutations in the ADSL gene lead to Adenylosuccinate Lyase Deficiency (ADSLD), a rare neurometabolic disorder characterized by the accumulation of toxic succinylpurines and symptoms such as psychomotor retardation, seizures, and autism (MedlinePlus, 2014). In oncology, ADSL is frequently overexpressed and acts as an oncogene in various malignancies, including prostate, breast, and colorectal cancers, where it supports the high nucleotide demand of rapidly proliferating cells (AACR, 2023; NIH, 2021). Consequently, the ADSL catalytic active site is a target for small-molecule inhibitors in cancer therapy and is also being explored as a selective antimicrobial target for pathogens like Mycobacterium tuberculosis (MDPI, 2021; NIH, 2025).

Other names

AdenylosuccinaseASLAMPSASASE

Competitive inhibition of the catalytic active site, preventing the conversion of SAICAR to AICAR and adenylosuccinate to AMP (MDPI, 2021; NIH, 2025).